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Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011 - pc
- 1. Update on Treatment for Lymphoma Lymphoma Support Ireland Meeting 19-02-2011 Dr. Greg Korpanty Medical Oncology Registrar Beaumont Hospital
- 7. CLP, common lymphoid precursor; BLB, pre-B lymphoblast; DN, CD4/CD8 double-negative pro-T cell; DP, CD4/CD8 double-positive pre-T cell; GC, germinal-center B cell; MC, mantle B cell; MZ, marginal zone B cell; NBC, naive B cell; PTC, peripheral T cell.
- 11. Histopathological classification Lymphoma Non-Hodgkin Lymphoma 85% Hodgkin Lymphoma 15% B-cell NHL 80% T-cell NHL 20%
- 13. New cases: 65,540 Deaths: 20,210
- 24. Rituximab
- 25. Rituximab
- 26. Bexxar, Zevalin
- 29. Bendamustine + Rituximab vs R-CHOP in Indolent NHL: AEs Rummel M, et al. ASH 2009. Abstract 405. Parameter Bendamustine + Rituximab R-CHOP P Value Grade 3/4 neutropenia, 10.7 46.5 < .0001 Grade 3/4 leukocytopenia, 12.1 38.2 < .0001 G-CSF use 4 20 < .0001 Infections, n 96 127 .0025 Erythema, n 42 23 .0122 Allergic skin reaction, n 40 15 .0003 Paresthesias, n 18 73 < .0001 Stomatitis 16 47 < .0001
- 30. GELA PRIMA Phase III Study: Rituximab Maintenance in FL CHOP x 6 + Rituximab x 8 CVP x 8 + Rituximab x 8 FCM x 6 + Rituximab x 8 Patients with previously untreated grade 1-3 FL (N = 1200) CR, PR RANDOMI ZED Maintenance Rituximab 375 mg/m 2 q2mo x 2 yrs Observation Available at: http://prima.gela.org.
- 31. Rituximab Maintenance for 2 Yrs: PRIMA Phase III Study Salles GA, et al. ASCO 2010. Abstract 8004. At 2 yrs, rituximab arm had significant improvements in time to next antilymphoma treatment and RR PFS 95% CI P Value Rituximab, % 82 (2 yrs) 78-86 < .0001 Observation, % 66 (2 yrs) 61-70 Grade 3/4 Adverse Events Rituximab Overall: 23% Neutropenia: 4% Infections: 4% Observation Overall: 16% Neutropenia: < 1% Infections: < 1%
- 33. Preliminary Analysis of Rituximab vs Watch and Wait in Asymptomatic FL Pts Ardeshna K, et al. ASH 2010. Abstract 6. Progression-free survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 1 2 3 4 5 Proportion of Patients Progression Free Yrs From Randomization 3-Yr PFS W + W: 33% R4: 60% R4 + RM: 81% W + W R4 R4 + RM Events 108 33 33 Pts 181 83 189
- 36. Rituximab ± Bortezomib in Relapsed, Rituximab-Naive or -Sensitive FL Coiffier B, et al. ASH 2010. Abstract 857. Rituximab 375 mg/m 2 Cycle 1: Days 1, 8, 15, 22 Cycles 2-5: Day 1 only Rituximab + Bortezomib Rituximab 375 mg/m 2 Cycle 1: Days 1, 8, 15, 22 Cycles 2-5: Day 1 only + Bortezomib 1.6 mg/m 2 Cycle 1: Days 1, 8, 15, 22 25 Wks Patients with relapsed, rituximab-naive or -sensitive FL (N = 670)
- 37. Results Coiffier B, et al. ASH 2010. Abstract 857. Response, n (%) Bort + Ritux (n = 315) Ritux (n = 324) P Value ORR 199 (63) 160 (49) < .001 CR 79 (25) 59 (18) .035 SD 78 (25) 120 (37) -- PD 38 (12) 44 (14) -- Overall durable response rate 159 (50) 124 (38) .002 Durable CR 76 (24) 54 (17) -- 100 90 80 70 60 50 40 30 20 10 0 48 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Patients Without Event (%) Mos Median PFS (95% CI) 11.0 mos (9.1-12.0) 12.8 mos (11.5-15.0) Rituximab: Bortezomib-rituximab : HR: 0.822 (0.681-0.991; P = .039)
- 40. Diffuse Large B-Cell Lymphoma (DLBCL)
- 42. CHOP(R) Chemotherapy C yclophosphamide (Cytoxan) H ydroxydaunorubicin (Adriamycin) O ncovin (vincristine) P rednisone R ituximab
- 44. LNH 03-2B Study: Results Récher C, et al. ASH 2010. Abstract 109. 3-Yr PFS 1.0 Survival Probability 0.8 0.6 0.4 0.2 0 0 12 24 36 48 60 72 Mos P = .0015; HR: 0.482 R-ACVBP R-CHOP 3-Yr OS 1.0 Survival Probability 0.8 0.6 0.4 0.2 0 0 12 24 36 48 60 72 Mos P = .0071; HR: 0.439 R-ACVBP R-CHOP
- 45. T-Cell Lymphoma
- 50. 1798 - 1866 Thomas Hodgkin
- 54. E2496: ABVD vs Stanford V ± Radiation Therapy in Advanced Hodgkin Lymphoma Gordon LI, et al. ASH 2010. Abstract 415. ABVD 6-8 cycles modified IFRT 36 Gy only in patients with massive mediastinal disease (n = 404) Stanford V - MOPPEBVCAD 12 wks’ chemotherapy, modified IFRT 36 Gy to sites > 5 cm in max transverse dimension (n = 408) *Defined as mass ≥ 1/3 maximum intrathoracic diameter on standing PA chest x-ray. Previously untreated patients with histologically proven HL, advanced or locally extensive disease, massive mediastinal adenopathy* (N = 812)
- 59. Novel Therapies Under Investigation in Lymphomas
- 63. Thank You
Editor's Notes
- Lymphoma is a very broad term.
- Findings from a recent trial conducted by Rummel and colleagues evaluating bendamustine and rituximab vs R-CHOP as first-line therapy for patients with advanced FL, MCL, and indolent NHL showed significantly higher complete response and progression-free survival among patients on bendamustine plus rituximab vs those on R-CHOP ( P = .0323 and P =.0002, respectively). Progression-free survival among patients with follicular lymphoma was significantly higher among patients receiving bendamustine plus rituximab therapy vs those on R-CHOP ( P = .02).
- Higher rates of grade 3/4 neutropenia and leukocytopenia were reported in the R-CHOP group, as well as use of G-CSF and alopecia ( P < .0001 for all comparisons). More patients receiving R-CHOP developed infections and peripheral neuropathy compared with those on bendamustine plus rituximab ( P = .0403 and P < .0001, respectively).
- In the phase III GELA PRIMA study, patients who achieved complete or partial response after initial therapy were randomly assigned to receive maintenance rituximab or observation for 2 years. The primary endpoint of this study was progression-free survival, and study endpoints were event-free survival and overall survival.
- Recently reported findings showed that patients on maintenance rituximab elicited a significantly higher 2-year PFS rate vs observation ( P < .0001) and also had response rates and improved time to next anti-lymphoma treatment. However, maintenance rituximab also was associated with higher rates of grade 3/4 neutropenia and infections.
- CI, confidence interval; FL, follicular lymphoma; HR, hazard ratio; M, maintenance; PFS, progression-free survival; R4, rituximab; RM, rituximab maintenance; W + W, watch and wait.
- Bendamustine was evaluated in a single-arm, phase III trial among patients with rituximab-refractory NHL. Bendamustine 120 mg/m 2 was given on Days 1 and 2 every 21 days for 6-8 cycles as long as response to stable disease was maintained. Primary endpoints of the study included overall response rates and duration of response, and secondary endpoints were progression-free survival and safety.
- Results showed overall response rates were 75% among patients who received at least one dose of bendamustine (n = 100), 88% among those who had at least a partial response to the previous treatment regimen (n = 51), and 64% among those who did not respond to the last regimen (n = 36). There were no significant differences in response rates by histology. Median PFS was reported to be 9.3 months, and median duration of response was 9.2 months.
- FL, follicular lymphoma; FLIPI, Follicular Lymphoma International Prognostic Index.
- Bort, bortezomib; CI, confidence interval; CR, complete response; HR, hazard ratio; IRC, Independent Review Committee; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; Ritux, rituximab; SD, stable disease.
- PN, peripheral neuropathy.
- CI, confidence interval; FDG; fluorodeoxyglucose; HR, hazard ratio; NR, not reported; PET-CT, positron emission tomography–computed tomography; PFS, progression-free survival.
- CNS, central nervous system; CR/CRu, complete response/unconfirmed complete response; FDS, disease-free survival; DLBCL, diffuse large B-cell lymphoma; EFS, event-free survival; IFM, ifosfamide; IT-MTX, intrathecal methotrexate; MTX, methotrexate; OS, overall survival; PFS, progression-free survival; R-ACVBP rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone; R-CHOP; rituximab plus cyclophosphamide, doxorubicin, prednisone, vincristine.
- FES, event-free survival; HR, hazard ratio; PFS, progression-free survival; R-ACVBP rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone; R-CHOP; rituximab plus cyclophosphamide, doxorubicin, prednisone, vincristine. .
- CR, complete response; Cru, unconfirmed complete response; IRC, independent review committee; PD, progressive disease; PR, partial response; PTCL, peripheral T-cell lymphoma; SD, stable disease.
- ABVD, bleomycin, dacarbazine, doxorubicin, vinblastine; HL, Hodgkin lymphoma; IFRT, involved-field radiation therapy; PA, posteroanterior.
- ABVD, bleomycin, dacarbazine, doxorubicin, vinblastine; CCR, complete response + clinical complete response; CR, complete response; FFS, failure-free survival; OS, overall survival; PD, progressive disease; PR partial response; SD, stable disease.
- ASCT, autologous stem cell transplantation; CR, complete response; ECOG, Eastern Cooperative Oncology Group; CR, complete response; OS, overall survival; PFS, progression-free survival; PR, partial response; PS, performance score; SD, stable disease.
- CR, complete response; HL, Hodgkin lymphoma; Inv., investigator; IRF, independent review facility; ORR, overall response rate; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease.
- BID, twice daily; NHL, non-Hodgkin’s lymphoma.
- CR, complete response; ORR, overall response rate; PR, partial response.